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Saudi Journal of Kidney Diseases and Transplantation
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EDITORIAL Table of Contents   
Year : 2008  |  Volume : 19  |  Issue : 3  |  Page : 329-345
Contribution of Inflammation to Vascular Disease in Chronic Kidney Disease Patients


Department of Clinical Science, Intervention and Technology, Karolinska Institute, Karolinska University Hospital at Huddinge, Stockholm, Sweden

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   Abstract 

Chronic kidney disease (CKD) is characterized by an exceptionally high mortality rate, much of which results from cardiovascular disease (CVD). Chronic low-grade inflammation, as evidenced by increased levels of pro-inflammatory cytokines and C-reactive protein (CRP), is a common feature of CKD and may cause atherosclerotic CVD through various pathogenetic mechanisms. Evidence suggests that persistent inflammation may also be a risk factor for progression of CKD, which may result in a vicious inflammation-driven circle. The causes of inflammation in CKD are multifactorial. The influence of various comorbidities may contribute to inflammation in the setting of progressive loss of renal function. Available data suggest that pro-inflammatory cytokines also play a central role in the genesis of the metabolic syndrome. There is a lack of epidemiological data on the prevalence and consequences of inflammation in relation to protein-energy wasting (PEW) and CVD in CKD patients from developing countries. The 'westernization' of nutritional intakes and changes of life style besides the high prevalence of chronic infections in developing countries are possible additive contributors to a high prevalence of inflammation, PEW and CVD among CKD patients. Also, genetic differences may affect inflammatory responses and nutritional status and, thus, the susceptibility to CVD in different regions.

Keywords: Inflammation, cardiovascular disease, wasting, chronic kidney disease, metabolic syndrome, developing countries

How to cite this article:
Suliman ME, Stenvinkel P. Contribution of Inflammation to Vascular Disease in Chronic Kidney Disease Patients. Saudi J Kidney Dis Transpl 2008;19:329-45

How to cite this URL:
Suliman ME, Stenvinkel P. Contribution of Inflammation to Vascular Disease in Chronic Kidney Disease Patients. Saudi J Kidney Dis Transpl [serial online] 2008 [cited 2019 Sep 21];19:329-45. Available from: http://www.sjkdt.org/text.asp?2008/19/3/329/40491

   Introduction Top


Inflammation is a process by which the body responds to invasion of an infectious agent, antigen challenge, and exposure to physical, chemical, or traumatic damage. Chronic inflammation is an inflammatory response of prolonged duration provoked by the persistent effect of a causative stimulus or damage in the tissue. In recent years, acute phase reactants have been studied as potential markers of more subtle and persistent sys­temic alterations labeled as chronic or persis­tent low-grade inflammation, which is now considered to be a major culprit in a broad range of pathological states, such as athero­sclerotic cardiovascular disease (CVD), obesity, diabetes mellitus (DM), protein energy wasting (PEW), ageing, and chronic kidney disease (CKD).

Prevalence of inflammation is high in CKD patients, as reflected by the elevated levels of acute phase reactants such as serum C­reactive protein (CRP), and other pro­inflammatory cytokines. [1],[2],[3] It has been recog­nized that about 30-50% of non-dialyzed, hemodialysis (HD), and peritoneal dialysis (PD) patients have serologic evidence of active inflammatory response with elevated serum levels of CRP. [4] The normal range of CRP is less than 2 mg/L in healthy indi­viduals. [5] In a study including 663 CKD stage 5 patients from Sweden, Germany and Italy, CRP was >3.4 mg/L in about 2/3 of the patients. [6] Furthermore, recent data from USA shows that 39% of 1761 HD patients had CRP levels ranging between 15-30 mg/L, and 29% had levels >30 mg/L. [7] Chronic low-grade inflammation is a common pheno­menon also in patients with stages 2-4 CKD. [8],[9],[10],[11] The sources of inflammation in CKD patients are not fully clear, but several factors may hold responsibility. In recent years, it has become evident that inflammation is among the strongest predictors of poor clinical outcome in CKD patients. Elevated plasma levels of pro-inflammatory cytokines, interleukin-1 (IL-1), IL-6, and tumor necrosis factor (TNF)-α are also associated with increased mortality. [2],[3]

The persistent review outlines the current knowledge of the sources and consequences of a chronic inflammatory state in the CKD population.


   Sources of inflammation Top


It is now well-recognized that uremia milieu is associated with a state of chronic low­grade inflammation. [12] Although multiple factors might be related, causes of inflamma­tion in CKD are still not well recognized; both non-dialysis related factors as well as the dialysis procedure per se may be respon­sible for the high prevalence of inflammation in stage 5 CKD patients.

Several lines of evidence suggest that renal function may have a crucial role in the acti­vity of the inflammatory process and reduction of kidney function per se is accompanied with an inflammatory response; i.e "uremic inflammation". CKD patients are affected by a chronic inflammatory state represented by elevated levels of positive acute phase proteins such as CRP. The increase of CRP appear to reflect generation of pro-inflammatory cytokines, such as IL-1, IL-6 and TNF-α, which are elevated in CKD patients, [3],[12],[13] and predict mortality. [2],[3],[14] Deterioration of renal function has been associated with a significant increase in serum cytokine levels, [15] and strong correlations between creatinine clearance and various cytokines and their soluble receptors have been demonstrated in non-dialyzed patients with varying degrees of renal failure. [16],[17] Bolton et al, [18] found in a multiple regression analysis that serum creatinine was the sole determinant of IL-6 levels in CKD patients. Moreover, Chung et al, [19] have recently demonstrated a significant association between markers of inflammation and changes in residual renal function in PD patients. Finally, reduced renal function may affect both TNF-α[20] and IL-1[21] clearance in nephroctomized rats. Hence, pro-inflammatory cytokines have been suggested to act as uremic toxins. [22],[23]

Moreover, several pathogenetic mechanisms plausibly contribute to direct activation of the inflammatory process under the influence of the unfriendly uremic milieu. [24],[25] For example, the kidney plays an important role in the metabolism of advanced glycation end­products (AGEs), production of reactive oxygen species (ROS), and development of oxidative damage, which potentially causes activation of mononuclear cells and stimu­lation of an inflammatory response. It has been hypothesized that retention of AGEs [26] and pro-oxidants [27] contribute to a pro­inflammatory milieu when renal function declines. Additional mechanisms by which a failing kidney function may promote infla­mmation include Sympathetic Overreactivity (and/or blunted vagal nerve activity) and reduced production of Specific Cytokine inhibitors, abbreviated as (SOCS). Since cholinergic anti-inflammatory pathway is a neural mechanism that inhibits local cytokine release, blunted vagal activity may lead to increased inflammatory activity. [28] Over­hydration, a frequent complication in CKD patients, may contribute to inflammation via bacterial or endotoxin translocation associated with severe gut edema and results in immunoactivation and increased inflammatory cytokine production. [29],[30]

Other non-dialysis-related causes that are associated with high levels of markers of inflammation include congestive heart failure, [29] atherosclerosis [31] and vascular calcifications. [32] Moreover, DM and hypertension are major causes of CKD. Elevated levels of CRP and IL-6 predicted the development of type-2 DM, and suggested a role for inflammatory process in the pathogenesis of this disease. [33] Low-grade chronic inflammation also plays a role in hypertension. Increases in arterial blood pressures and pulse pressure were associated with elevated levels of IL-6 and intercellular adhesion molecule inhibitors (ICAM-1). [34],[35] In addition, aging among CKD patients is also associated with several diseases that may be linked to changes in the immune response. [36]

Apart from non-infectious causes of infla­mmation, it should be emphasized that various chronic persistent infections such as Chlamydia pneumoniae, [37] Helicobacter pylori [38] and periodontal diseases [39] may also contribute to high prevalence of inflammation in CKD patients. In fact, as reported in the HEMO study, there were 1698 infection-related hospitalizations, yielding a 35% annual rate. [40] In HD patients, high levels of IgG antibodies to bacterial species, (associated with destruct­tive periodontal diseases) were associated with elevated CRP levels. [39] In PD patients, Aguilera et al, [38] observed an association of H. pylori infection with anorexia, inflamma­tion and PEW. Hepatitis may be yet another cause of chronic inflammation in HD patients. Moreover, serum levels of hepatocyte growth factor, a pleiotropic cytokine involved in tissue protection and repair of the endo­thelium in various organ systems, were increased in hepatitis C virus seropositive patients. [41]

The increased levels of inflammatory markers in dialysis patients suggests that the dialysis procedure, i.e. the extracorporeal circulation of blood [42] and bioincompatible PD solutions, [43] may contribute to inflammation. In HD patients, the use of bioincomeatible membranes, [44],[45] nonsterile dialysateand backleak of dialysate across the dialysis membrane [47] have been associated with an inflammatory response. Vascular access in HD, especially grafts and catheters, and various factors associated with the PD procedure such as peritonitis, bioincompatible dialysis fluids, and percutaneous PD catheter infections, provide a portal for entry for microorganisms, which induces inflammation in dialysis patients. This supports the concept that the repetitive cytokine response to dialysis procedure is additive to the inflammatory syndrome associated with uremia.


   Inflammation as a cause of CKD progression Top


As discussed above, deterioration of renal function is associated with amplification of the inflammatory state. [8],[10],[48] Some studies reported lack of association between impair­ment of renal function and increase of CRP in non-diabetic CKD patients, [49] while others demonstrated a state of systemic infla­mmation that may promote progression of renal disease. [50],[51] Stuveling et al, [50] studied 7317 non-diabetic patients with high CRP levels and found association with prog­ression of CKD. Moreover, two putative inflammatory markers, neopterin and pento­sidine, predicted doubling of serum creatinine in type-2 diabetic patients. [51]

There may be several reasons why elevated CRP levels may be associated with progression of CKD. First, it is possible that increase in CRP may reflect a local infla­mmatory response in the kidney. Indeed, deleterious local effects of CRP per se have been shown as it localizes in kidney tissue with glomerular disease, [52] attenuates nitric oxide (NO) production, and upregulates angiotensin I receptors in the vascular smooth muscle cells. [53] In this respect, it is of interest that inflamed kidneys represent an unknown site for CRP formation in vivo. [52] Second, as inflammation is now believed to represent one underlying mechanism that results in atherosclerosis, [31],[54] glomerulosclerosis is a disease process with a striking similarity to atherosclerosis. [55] Hitherto, it has been docu­mented that CRP has effects on endothelial cells [56] through inhibition of endothelial progenitor cell function and cell differen­tiation, [57] which includes activation of nuclear factor kappa B (NF-KB), [58] release of the potent endothelial-derived contracting factor endothelin-1 [59] and decreased eNOS expre­ssion and activity in aortic endothelial cells, [60] an effect that may theoretically promote progression of CKD. Thus, it is plausible that inflammation may cause a decline of renal function by promoting endothelial dysfunction, atherosclerosis, and glomerular damage. Finally, anti-inflammatory treatment strategies revealed a beneficial effect in pre­serving renal function. For instance, pento­xifylline, a TNF inhibitor, attenuated renal disease progression in rats. [61] Also, randomized controlled studies angiotensin-converting enzyme inhibitors manifested significant anti­inflammatory properties in CKD [62] and reduced the rate of decline of residual renal function in PD patients. [63] Moreover, pravastatin, which may have significant anti­inflammatory properties in CKD, has been demostrated to slow renal function loss in individuals with moderate to severe CKD. [64]


   Inflammation as a cause of protein­ energy wasting Top


PEW is highly prevalent (34-65%) in CKD, and is considered among the strongest predictors of death in this patient population. Although many factors contribute to im­paired nutritional status in CKD patients, inflammation is one of the most important ones. Furthermore, PEW and inflammation are strongly interrelated in the clinical setting. [65],[66] Hypoalbuminemia, which is common in CKD patients and usually consequent to PEW, is strongly associated with inflammation. [2],[67] Kaysen et al, [68] demonstrated that CRP was the primary predictor of serum albumin levels in HD patients. Indeed, increase in the levels of pro-inflammatory cytokines is related to high prevalence of PEW and hypoalbuminemia in CKD patients. [2],[69],[70]

Although the mechanism(s) by which elevated serum levels of pro-inflammatory cytokines cause anorexia are not clear. The effects of cytokines may result from their catabolic effects on protein metabolism, direct action on the gastrointestinal system, and indirect effects mediated by cytokines on the central nervous system. [71] One important mechanism by which elevated levels of pro­inflammatory cytokines may mediate PEW is by increasing protein hydrolysis and muscle protein breakdown via activation of NF­-kB [72] and/or the ubiquitin-proteasome pro­teolytic system. [73] In addition, IL-6 may stimu­late muscle protein breakdown and promote inflammation related wasting. [74] Another important effect by which elevated levels of pro-inflammatory cytokines may cause PEW is suppression of appetite and eating behavior. [75] Moreover, pro-inflammatory cyto­kines may also inhibit appetite by decreasing gastrointestinal motility, modifying gastric secretion, and eliciting taste aversion. [71] Also, inflammation has been speculated to mediate anorexia through the anorexic hormone leptin which, at least in animal experiments, has been shown to be upregulated by pro­inflammatory cytokines. [76] Accordingly, anorectic HD patients presented with high levels of CRP and IL-6 [77] and increased circulating levels of IL-6 have been related to various markers of wasting in CKD patients. [78] This indicates an important role for this cytokine in the development of PEW and muscle catabolism in CKD. [79] Furthermore, IL-6 inhibits the secretion of insulin like growth factor (IGF)-1, which results in the worsening of the PEW. [80]

Previously, we proposed two types of PEW in CKD patients; [81] Type-1 PEW, in which inadequate nutritional intake is the predominant cause and Type-2 PEW, in which inflammation and co-morbid disease are the predominant causes. Other terms have also been suggested including the "Malnutrition Inflammation-Atherosclerosis syndrome "[82] to underscore the intriguing association between PEW/inflammation and vascular disease. Studies demonstrated higher pre­valence of PEW and hypoalbuminemia in CKD patients with than without CVD. [1],[82] Although it is far from clear how CVD and PEW are interrelated, it has been proposed that inflammation might be one factor linking PEW, CVD, and mortality. [82],[83]


   Inflammation and cardiovascular disease Top


Several lines of evidence have linked atherogenesis to inflammation. [31],[54] Atherosclerotic lesion is characterized by the accumulation of lipid particles and cells of the immune system in subendothelial layers. [84] Cytokines are secreted by immune cells within the atherosclerotic plaque [85] and endothelial dysfunction is characterized by predominance of pro-inflammatory over anti-inflammatory phenotypes. [31],[54] Ultimately, the inflammatory process in the athero­sclerotic vessels may result in increased circulating levels of inflammatory cytokines and acute-phase reactants. [54] One of the most compelling evidence for the role of the immune system in atherogenesis comes from specific transgenic and knockout mice. [86],[87],[88] Furthermore, abundant in vitro data have emerged revealing that CRP has pro­inflammatory and pro-thrombotic effects in vitro. [89],[90] For example, Torzewski et al, [91] found that CRP deposited in the arterial wall of early atherosclerotic lesions. Moreover, CRP was demonstrated to co-localize with complement in heart tissue during acute myocardial infarction, leading to the hypo­thesis that CRP may directly cause tissue damage. [92] Furthermore, CRP can induce adhesion molecule expression, suggesting a direct pro-inflammatory effect of CRP on human endothelial cells. [90] CRP has also been shown to reduce endothelial progenitor cell number and function, thereby reduces the balance between cardiovascular repair and regeneration. [57] It should also be pointed out that acute-phase reactants other than CRP may contribute to an accelerated athero­sclerotic process. For example, inflammation reduces the circulating levels of potent inhibitors of vascular calcification, such as fetuin-A, matrix Gla protein (MGP), and osteoprotegrin, and contributes to vascular calcification. [93] In addition, the acute-phase protein pentraxin-3 (a long pentraxin), an inflammatory mediator produced by endo­thelial cells, may have a role in atherogenesis. [94]

The association between inflammation and CVD is evident in both non-renal and renal populations. In fact, even small increases in the circulating levels of IL-6 [95] and CRP [96] are associated with CVD in non-renal patient groups. Several epidemiologic studies have demonstrated that elevated levels of CRP, [97],[98] Pentraxin-3, [99] IL-6 [100],[101] and soluble adhesion molecules, such as ICAM-1 and VCAM­1, [102] are associated with CVD in CKD patients.


   Inflammation and the metabolic syndrome Top


The metabolic syndrome is a cluster of several cardiovascular risk factors that include insulin resistance, glucose intolerance/DM, hypertension, dyslipidemia, obesity and increased circulating levels of pro inflamma­tory and pro-thrombotic markers. Recently, Chen et al, [103] examined the relationship of the metabolic syndrome with CKD in the NHANES III cohort. They found that the odd risk (OR) for developing CKD over time was 2.6 for individuals with the metabolic syndrome in comparison to individuals without the metabolic syndrome. Moreover, the OR increased with increasing components of the metabolic syndrome and this relation­ship persisted even after exclusion of indi­viduals with DM. Similarly, Kurella et al, [104] demonstrated that the metabolic syndrome was an independent risk factor for incidence of CKD in the non-diabetic population. Another study reported a higher risk for microalbuminuria in individuals with the metabolic syndrome. [105] Insulin resistance and hyperinsulinemia in the absence of DM predicted the development of CKD. [106] In addition, the metabolic syndrome predisposed for CKD in the absence of hyperglycemia or DM, and independent of hypertension. [107] Wu et al, [108] demonstrated high expression of inflammatory cytokine genes as well as genes associated with insulin resistance and lipid metabolism in glomeruli of patients with obesity-related glomerulopathy compared with gender- and age-matched glomeruli of control donor kidneys.

The hallmark of the metabolic syndrome is insulin resistance. Since insulin is an anti­inflammatory hormone, resistance to its action may explain why obesity/metabolic syndrome is a pro-inflammatory state. [109],[110] In addition, inflammatory mediators, such as TNF-α, have been shown to mediate insulin resistance. [111] Thus, TNF-α decreases insulin-stimulated storage of glucose [112] and when adminis­tered to animals can induce insulin resistance, [112] whereas its neutralization with thiazolidine­diones can improve insulin sensitivity. [113] Further support for a direct pathogenic role of TNF-α in the development of insulin resistance stems from studies demonstrating a relationship between TNF-α and insulin sensitivity in other insulin-resistant patient groups, such as in patients with obesity [114] and essential hypertension. [115] Nevertheless, insulin resistance and inflammation may interact in a vicious cycle, and the initial culprit is usually difficult to ascertain. Indeed, several different features of the metabolic syndrome, such as increased body mass index, [116] serum lipid levels, and fasting glucose levels [117] are linked to inflammation, and almost all components of the metabolic syndrome are associated with systemic low­grade inflammation. [118] Plasma concentrations of inflammatory markers, such as CRP, IL-6, TNF-α and resistin are elevated in patients with the metabolic syndrome, whereas the levels of other adipokines, such as adiponectin and leptin are reduced. [109],[110]

Although most of the circulating IL-6 is secreted from activated macrophages and lymphocytes. Other tissues, such as adipose tissue, may also contribute to the production of IL-6. It has been estimated that about 20% of the circulating IL-6 originates from fat tissue. [119] Moreover, a significant amount of the circulating TNF-α comes from macro­phages present in the adipose tissue. [120] Clinical studies in type-2 diabetic patients revealed correlations between fat mass and pro-inflammatory cytokines. [121] Several studies have shown that adipose tissue, especially visceral adipose tissue, is a major source of cytokine secretion in the metabolic syndrome and that inflammatory cells invade adipose tissue early in obesity. [120],[122] More recently, inflammation was linked to obesity and the metabolic syndrome in patients with CKD. [123],[124],[125] In the NHANES III cohort Ramkumar et al, [126] found that the presence of the metabolic syndrome was associated with greater odds for inflammation for various levels of crea­tinine clearance. [127] In accordance, truncal fat mass was associated with inflammatory markers, including IL-6 and CRP in incident dialysis patients. [79] On the other hand, a functional and molecular overlap between fat cells and macrophages have been reported recently. [128] In non-renal patients, it has been shown that macrophages infiltrating adipose tissue form an important source of circulating pro-inflammatory cytokines. [129],[130] In CKD patients, Axelsson et al, [131] demonstrated that increasing fat mass was associated with increasing levels of sCD163, a circulating marker of macrophages that is associated with inflammatory biomarkers. In summary, it is evident from the preceding discussion that almost all components of the metabolic syndrome are associated with low-grade systemic inflammation. [118]


   Inflammation predicts poor outcome in CKD Top


Several studies have demonstrated that high levels of CRP predict outcome in the general population. [96],[132],[133],[134] Numerous studies have shown that inflammation predicts both all-cause and cardiovascular mortality in CKD patients. [97],[135],[136],[137],[138],[139] Moreover, persistent, rather than occasional, high CRP predicts worse survival in dialysis patients [140] and elevated CRP levels observed after a HD session were associated with both cardiac hypertrophy [141] and a higher mortality risk. [142] In PD patients, an elevated CRP was shown to be an independent predictor of nonfatal myocardial infarction [143] and increased inci­dence of CVD. [138] Recent data from the MDRD study showed that both high CRP and hypoalbuminemia predicted poor outcome in CKD stages 3-4. [44],[145] Further support linking inflammation to poor outcome in CKD stems from large studies in HD patients, demonstrating an association between the neutrophil count and mortality. [146],[147] Moreover, other less commonly measured inflammatory markers, such as Pentraxin­-3, [99] IL-6, [2],[78],[148] soluble adhesion molecules [102] and fibrinogen, [149] have been illustrated to predict mortality in CKD population. The results of a large cohort of US dialysis patients demonstrated that septicemia was associated with increased cardiovascular death risk [150] also support a role of inflammation in atherogenesis.


   A Global view on inflammation in CKD Top


While a large part of the CKD population is located in developing countries, most of the accessible information on CVD in CKD is based on studies carried out in Indus­trialized western and in some developed Asian countries. Although information on the prevalence and the impact of low-grade inflammation and associated PEW in CKD is poorly documented in developing countries, high prevalence of these complications could be anticipated.

To the best of our knowledge, no studies analyzing the prevalence of inflammation, PEW and atherosclerosis in CKD patient are yet available from the Arab World. However, genetic, patient characteristics and socio­economic factors (i.e. patient referral, etiology of renal diseases, availability of dialysis facilities, transplantation rate, diet, tobacco smoking, and physical activity) may contribute to differences in the prevalence of infla­mmation, PEW and CVD around the world. The characteristics of the population regarding primary renal disease, time of referral, and dialysis conditions may differ drastically around the world. While it is clear that DM and hypertension are already the leading causes of CKD in industrialized countries, a growing number of patients start dialysis as a consequence of these age-related diseases also in developing countries. A high preva­lence of DM has been reported in the Arab World. [151],[152] Like in the rest of the world, DM is a major cause of renal failure in Saudi Arabia [153] and in other Arabic countries. [154]

Obesity is another health problem in the Arab world that may predispose to insulin resistance and inflammation. It has been reported that at least one third of the Arab population can be defined as being obese. [155] Although few studies evaluated prevalence rate of hypertension in the Arab world, the available data suggest high prevalence of the disease. [156] Chronic glomerulonephritis and interstitial nephritis are currently the major causes of CKD in developing countries due to high rate of infection and inflammation that affect the kidneys. [157]

Underdeveloped and developing countries still face the problem of inadequate diet and inappropriate sanitary infrastructures, resulting in high prevalence of chronic infectious diseases, such as Chlamydia pneumoniae, Helicobacter pylori, HIV, and periodontal pathogens, all of which may represent signi­ficant etiological factors linking inflammation to atherogenesis. Other chronic infections that are highly prevalent in developing countries are tuberculosis, hepatitis B and C, and malaria. In addition, the "Westernization" of life style that may change diets, acquire tobacco smoking habit, decrease in physical activity, and contribute to increasing CVD in developing countries, [158] possibly through various mechanisms including inflammation.

The socioeconomic changes affecting the availability of dialysis therapy have caused a dramatic change in prevalence of elderly and diabetic patients on dialysis. [159] Obviously, the introduction of modern HD machines, water treatment and wider use of erythro­poietin has influenced positively both the quality of life and outcome. [159] Indeed, Jondeby et al, [153] reported that the degree of rehabili­tation has largely improved due to the techno­logical advances in dialysis delivery among HD patients in Saudi Arabia.

Generally, high prevalence rates of comorbi­dities indirectly suggest increased prevalence of chronic low-grade inflammation among CKD patients in the Arab world. The current knowledge on chronic low-grade inflamma-tion, PEW, their impact on CVD, and survival in CKD patients is mainly derived from industrialized western countries, and the applicability of the results to populations from other world regions is unknown. Accordingly, regional and comparative inter­regional studies focusing on the etiology and prevalence of inflammation and its relation­ship with PEW and CVD are warranted to define efficient strategies for the prevention and treatment of the unacceptably high car­diovascular mortality rate in CKD patients around the world.


   Conclusion Top


Chronic low-grade inflammation is a common feature of CKD and may cause atherosclerotic CVD through various pathogenetic mecha­nisms. Although the acute-phase reaction may simply reflect the underlying CVD, it may also directly cause vascular injury. Available evidences suggest that persisted low-grade inflammation may pre-dispose to be one factor for impairment of renal function. The causes of inflammation in CKD are definitely multi­factorial. Available data suggest that pro­inflammatory cytokines may play a central role in the genesis of the metabolic syndrome. There is a lack of epidemiological data on the prevalence and consequences of inflammation from the developing countries. It is possible that westernization of nutritional habits and life style besides high prevalence of chronic infections in developing countries contribute to high prevalence of inflammation in CKD patients. Moreover, genetic differences may affect inflammatory responses, nutritional status, and susceptibility to CVD in different regions of the world.

 
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Correspondence Address:
Mohamed E Suliman
Department of Renal Medicine, K56 Karolinska University Hospital at Huddinge 141 86 Stockholm
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